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Creatine and α-lipoic acid improved behavioral parameters of depression induced by dexamethasone in mice

Yıl 2021, , 65 - 73, 01.06.2021
https://doi.org/10.52794/hujpharm.902264

Öz

Objective: Corticosterone treatment in mice impairs mitochondrial function, decreases energy production in the brain, and induces depressive-like behaviors. Creatine (Crt) is vital for energy homeostasis in the brain. Alpha-lipoic acid (ALA) improves mitochondrial function and reduces oxidative stress. The aim was investigating the effect of Crt and ALA following dexamethasone (Dexa) induced depression in mice model of despair.
Methods: Female mice (22±3 g) were experimented. Dexa (15 mcg/kg, SC) injected for a week, Crt was inserted in animals’ diet, and ALA (25, 50 mg/kg) injected IP. After the locomotor test, behavioral parameters of depression, including immobility time during the forced swimming test (FST), and anhedonia during the sucrose preference test were evaluated. Results: There was not important changes during the locomotor test. Dexa increased the immobility time during the FST (154 ± 6.3 s vs control 119±5.5 s, p<0.05). Crt 2 %, reduced immobility time (89 ± 7 s vs normal diet 125 ± 4.7 s, p<0.01), ALA (50 mg/kg) reduced the immobility time (88 ± 15 vs control 134±8 s, p<0.05). While, Crt and ALA co-administration with Dexa reduced the immobility time during the FST. The results of the sucrose preference test were in line with FST, since Crt and ALA increased the sucrose preference when administered together with Dexa.
Conclusion: Improvement of behavioral parameters in mice treated with Crt and ALA clearly indicates their effect on preventing Dexa depressive-like behaviors. Apart from possible influence on mitochondria, modulation in the neurotransmitter system may be involved in their antidepressant effects.

Destekleyen Kurum

School of Pharmacy and Pharmaceutical Sciences Research Council

Proje Numarası

396903

Teşekkür

This work was supported by the School of Pharmacy and Pharmaceutical Sciences Research Council (grant number 396903, 1/15/2018), Isfahan University of Medical Sciences.

Kaynakça

  • 1-Manji H, Kato T, Di Prospero NA, Ness S, Beal MF, Krams M, et al. Impaired mitochondrial function in psychiatric disorders. Nat Rev Neurosci. 2012;13(5): 293-307.
  • 2-Dean J, Keshavan M. The neurobiology of depression: An integrated view. Asian J Psychiatr. 2017; 27: 101-111.
  • 3-Sonino N, Fava GA, Raffi AR, Boscaro M, Fallo F. Clinical correlates of major depression in Cushing’s disease. Psychopathology. 1998; 31(6): 302-306.
  • 4-Safaeian L, Hajhashemi V, Javanmard SH, Naderi HS. The effect of protocatechuic acid on blood pressure and oxidative stress in glucocorticoid-induced hypertension in rat. Iran J Pharm Res. 2016;15(Suppl): 83-91.
  • 5-Brown ES, Woolston DJ, Frol A, Bobadilla L, Khan DA, Hanczyc M, et al. Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy. Biol Psychiatry. 2004; 55(5): 538-545.
  • 6-Mesripour A, Rakhshankhah P. A synbiotic mixture ameliorated depressive behavior induced by dexamethasone or water avoidance stress in mice model. Turk J Pharm Sci. 2021;18(1):21-27
  • 7- Zhao Y, Ma R, Shen J, Su H, Xing D, Du L. A mouse model of depression induced by repeated corticosterone injections. Eur J Pharmacol. 2008; 581(1-2): 113-120.
  • 8-Rezin GT, Cardoso MR, Gonçalves CL, Scaini G, Fraga DB, Riegel RE, et al. Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression. Neurochem Int. 2008; 53(6-8): 395-400.
  • 9-Allen J, Romay-Tallon R, Brymer KJ, Caruncho HJ, Kalynchuk LE. Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression. Front Neurosci. 2018; 12: 386. doi: 10.3389/fnins.2018.00386. eCollection 2018.
  • 10-Petrosillo G, Matera M, Casanova G, Ruggiero FM, Paradies G. Mitochondrial dysfunction in rat brain with aging: involvement of complex I, reactive oxygen species and cardiolipin. Neurochem Int. 2008; 53(5):126-131.
  • 11-Stanyer L, Jorgensen W, Hori O, Clark JB, Heales SJ. Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction. Neurochem Int. 2008; 53(3-4): 95-101.
  • 12-Klinedinst NJ, Regenold WT. A mitochondrial bioenergetic basis of depression. J Bioenerg Biomembr. 2015; 47(1-2): 155-171.
  • 13-Madrigal JL, Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Rodrigo J, et al. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology. 2001; 24(4): 420-429.
  • 14-Andres RH, Ducray AD, Schlattner U, Wallimann T, Widmer HR. Functions and effects of creatine in the central nervous system. Brain Res Bull. 2008; 76(4): 329-343.
  • 15-Brustovetsky N, Brustovetsky T, Dubinsky JM. On the mechanisms of neuroprotection by creatine and phosphocreatine. J Neurochem. 2001; 76(2): 425-534.
  • 16-Takahashi H, Bungo Y, Mikuni K. The aqueous solubility and thermal stability of α-lipoic acid are enhanced by cyclodextrin. Biosci Biotechnol Biochem. 2011; 75(4): 633-637.
  • 17-Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-α-lipoic acid. Proc Natl Acad Sci USA. 2002; 99(4): 2356-2361.
  • 18-Salazar MR. Alpha lipoic acid: a novel treatment for depression. Med Hypotheses. 2000; 55(6): 510-512.
  • 19-Cryan JF, Markou A, Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci. 2002; 23(5): 238-245.
  • 20-Strekalova T, Spanagel R, Bartsch D, Henn FA, Gass P. Stress-induced anhedonia in mice is associated with deficits in forced swimming and exploration. Neuropsychopharmacology. 2004; 29: 2007–2017.
  • 21-Allen PJ, D'Anci KE, Kanarek RB, Renshaw PF. Chronic creatine supplementation alters depression-like behavior in rodents in a sex-dependent manner. Neuropsychopharmacology. 2010; 35(2): 534-546.
  • 22-Liu W, Zhou C. Corticosterone reduces brain mitochondrial function and expression of mitofusin, BDNF in depression-like rodents regardless of exercise preconditioning. Psychoneuroendocrinology. 2012; 37(7):1057-1070.
  • 23- Ulrich-Lai YM, Fulton S, Wilson M, Petrovich G, Rinaman L. Stress exposure, food intake and emotional state. Stress. 2015;18(4):381-399.
  • 24-Matthews RT, Ferrante RJ, Klivenyi P, Yang L, Klein AM, Mueller G, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol. 1999;157(1):142-149.
  • 25-Klivenyi P, Gardian G, Calingasan NY, Yang L, Beal MF. Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. J Mol Neurosci. 2003; 21(3): 191-198.
  • 26-Hadjicharalambous M, Kilduff LP, Pitsiladis YP. Brain serotonin and dopamine modulators, perceptual responses and endurance performance during exercise in the heat following creatine supplementation. J Int Soc Sports Nutr. 2008; 5(1):14.
  • 27- Cunha MP, Pazini FL, Oliveira Á, Bettio LEB, Rosa JM, Machado DG, et al. The activation of α1-adrenoceptors is implicated in the antidepressant-like effect of creatine in the tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 44: 39-50.
  • 28- Sapolsky RM. The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry. 2000; 48(8): 755-765.
  • 29-De Sousa CN, Meneses LN, Vasconcelos GS, Silva MC, da Silva JC, Macêdo D, et al. Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: emphasis on the neurotrophic hypothesis of depression. Psychiatry Res. 2015; 230(2): 211-219.
  • 30-Silva MC, de Sousa CN, Gomes PX, de Oliveira GV, Araújo FY, Ximenes NC, et al. Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016; 64: 142-148.
  • 31-Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychoph. 2008; 11(6): 851-876
  • 32-Carlsson A, Lindqvist M. The effect of L-tryptophan and some psychotropic drugs on the formation of 5-hydroxytryptophan in the mouse brain in vivo. J Neural Transm. 1972; 33(1): 23-43.

Creatine and α-lipoic acid improved behavioral parameters of depression induced by dexamethasone in mice

Yıl 2021, , 65 - 73, 01.06.2021
https://doi.org/10.52794/hujpharm.902264

Öz

Objective: Corticosterone treatment in mice impairs mitochondrial function, decreases energy production in the brain, and induces depressive-like behaviors. Creatine (Crt) is vital for energy homeostasis in the brain. Alpha-lipoic acid (ALA) improves mitochondrial function and reduces oxidative stress. The aim was investigating the effect of Crt and ALA following dexamethasone (Dexa) induced depression in mice model of despair.
Methods: Female mice (22±3 g) were experimented. Dexa (15 mcg/kg, SC) injected for a week, Crt was inserted in animals’ diet, and ALA (25, 50 mg/kg) injected IP. After the locomotor test, behavioral parameters of depression, including immobility time during the forced swimming test (FST), and anhedonia during the sucrose preference test were evaluated. Results: There was not important changes during the locomotor test. Dexa increased the immobility time during the FST (154 ± 6.3 s vs control 119±5.5 s, p<0.05). Crt 2 %, reduced immobility time (89 ± 7 s vs normal diet 125 ± 4.7 s, p<0.01), ALA (50 mg/kg) reduced the immobility time (88 ± 15 vs control 134±8 s, p<0.05). While, Crt and ALA co-administration with Dexa reduced the immobility time during the FST. The results of the sucrose preference test were in line with FST, since Crt and ALA increased the sucrose preference when administered together with Dexa.
Conclusion: Improvement of behavioral parameters in mice treated with Crt and ALA clearly indicates their effect on preventing Dexa depressive-like behaviors. Apart from possible influence on mitochondria, modulation in the neurotransmitter system may be involved in their antidepressant effects.

Proje Numarası

396903

Kaynakça

  • 1-Manji H, Kato T, Di Prospero NA, Ness S, Beal MF, Krams M, et al. Impaired mitochondrial function in psychiatric disorders. Nat Rev Neurosci. 2012;13(5): 293-307.
  • 2-Dean J, Keshavan M. The neurobiology of depression: An integrated view. Asian J Psychiatr. 2017; 27: 101-111.
  • 3-Sonino N, Fava GA, Raffi AR, Boscaro M, Fallo F. Clinical correlates of major depression in Cushing’s disease. Psychopathology. 1998; 31(6): 302-306.
  • 4-Safaeian L, Hajhashemi V, Javanmard SH, Naderi HS. The effect of protocatechuic acid on blood pressure and oxidative stress in glucocorticoid-induced hypertension in rat. Iran J Pharm Res. 2016;15(Suppl): 83-91.
  • 5-Brown ES, Woolston DJ, Frol A, Bobadilla L, Khan DA, Hanczyc M, et al. Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy. Biol Psychiatry. 2004; 55(5): 538-545.
  • 6-Mesripour A, Rakhshankhah P. A synbiotic mixture ameliorated depressive behavior induced by dexamethasone or water avoidance stress in mice model. Turk J Pharm Sci. 2021;18(1):21-27
  • 7- Zhao Y, Ma R, Shen J, Su H, Xing D, Du L. A mouse model of depression induced by repeated corticosterone injections. Eur J Pharmacol. 2008; 581(1-2): 113-120.
  • 8-Rezin GT, Cardoso MR, Gonçalves CL, Scaini G, Fraga DB, Riegel RE, et al. Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression. Neurochem Int. 2008; 53(6-8): 395-400.
  • 9-Allen J, Romay-Tallon R, Brymer KJ, Caruncho HJ, Kalynchuk LE. Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression. Front Neurosci. 2018; 12: 386. doi: 10.3389/fnins.2018.00386. eCollection 2018.
  • 10-Petrosillo G, Matera M, Casanova G, Ruggiero FM, Paradies G. Mitochondrial dysfunction in rat brain with aging: involvement of complex I, reactive oxygen species and cardiolipin. Neurochem Int. 2008; 53(5):126-131.
  • 11-Stanyer L, Jorgensen W, Hori O, Clark JB, Heales SJ. Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction. Neurochem Int. 2008; 53(3-4): 95-101.
  • 12-Klinedinst NJ, Regenold WT. A mitochondrial bioenergetic basis of depression. J Bioenerg Biomembr. 2015; 47(1-2): 155-171.
  • 13-Madrigal JL, Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Rodrigo J, et al. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology. 2001; 24(4): 420-429.
  • 14-Andres RH, Ducray AD, Schlattner U, Wallimann T, Widmer HR. Functions and effects of creatine in the central nervous system. Brain Res Bull. 2008; 76(4): 329-343.
  • 15-Brustovetsky N, Brustovetsky T, Dubinsky JM. On the mechanisms of neuroprotection by creatine and phosphocreatine. J Neurochem. 2001; 76(2): 425-534.
  • 16-Takahashi H, Bungo Y, Mikuni K. The aqueous solubility and thermal stability of α-lipoic acid are enhanced by cyclodextrin. Biosci Biotechnol Biochem. 2011; 75(4): 633-637.
  • 17-Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-α-lipoic acid. Proc Natl Acad Sci USA. 2002; 99(4): 2356-2361.
  • 18-Salazar MR. Alpha lipoic acid: a novel treatment for depression. Med Hypotheses. 2000; 55(6): 510-512.
  • 19-Cryan JF, Markou A, Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci. 2002; 23(5): 238-245.
  • 20-Strekalova T, Spanagel R, Bartsch D, Henn FA, Gass P. Stress-induced anhedonia in mice is associated with deficits in forced swimming and exploration. Neuropsychopharmacology. 2004; 29: 2007–2017.
  • 21-Allen PJ, D'Anci KE, Kanarek RB, Renshaw PF. Chronic creatine supplementation alters depression-like behavior in rodents in a sex-dependent manner. Neuropsychopharmacology. 2010; 35(2): 534-546.
  • 22-Liu W, Zhou C. Corticosterone reduces brain mitochondrial function and expression of mitofusin, BDNF in depression-like rodents regardless of exercise preconditioning. Psychoneuroendocrinology. 2012; 37(7):1057-1070.
  • 23- Ulrich-Lai YM, Fulton S, Wilson M, Petrovich G, Rinaman L. Stress exposure, food intake and emotional state. Stress. 2015;18(4):381-399.
  • 24-Matthews RT, Ferrante RJ, Klivenyi P, Yang L, Klein AM, Mueller G, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol. 1999;157(1):142-149.
  • 25-Klivenyi P, Gardian G, Calingasan NY, Yang L, Beal MF. Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. J Mol Neurosci. 2003; 21(3): 191-198.
  • 26-Hadjicharalambous M, Kilduff LP, Pitsiladis YP. Brain serotonin and dopamine modulators, perceptual responses and endurance performance during exercise in the heat following creatine supplementation. J Int Soc Sports Nutr. 2008; 5(1):14.
  • 27- Cunha MP, Pazini FL, Oliveira Á, Bettio LEB, Rosa JM, Machado DG, et al. The activation of α1-adrenoceptors is implicated in the antidepressant-like effect of creatine in the tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 44: 39-50.
  • 28- Sapolsky RM. The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry. 2000; 48(8): 755-765.
  • 29-De Sousa CN, Meneses LN, Vasconcelos GS, Silva MC, da Silva JC, Macêdo D, et al. Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: emphasis on the neurotrophic hypothesis of depression. Psychiatry Res. 2015; 230(2): 211-219.
  • 30-Silva MC, de Sousa CN, Gomes PX, de Oliveira GV, Araújo FY, Ximenes NC, et al. Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016; 64: 142-148.
  • 31-Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychoph. 2008; 11(6): 851-876
  • 32-Carlsson A, Lindqvist M. The effect of L-tryptophan and some psychotropic drugs on the formation of 5-hydroxytryptophan in the mouse brain in vivo. J Neural Transm. 1972; 33(1): 23-43.
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri
Bölüm Research Articles
Yazarlar

Azadeh Mesripour

Khashayar Musavie Bu kişi benim

Valiollah Hajhashemi Bu kişi benim

Proje Numarası 396903
Yayımlanma Tarihi 1 Haziran 2021
Kabul Tarihi 20 Mayıs 2021
Yayımlandığı Sayı Yıl 2021

Kaynak Göster

Vancouver Mesripour A, Musavie K, Hajhashemi V. Creatine and α-lipoic acid improved behavioral parameters of depression induced by dexamethasone in mice. HUJPHARM. 2021;41(2):65-73.